CN1130233C

CN1130233C - INhalation device and method

Info

Publication number: CN1130233C
Application number: CN96195151A
Authority: CN
Inventors: 迈克尔·T·谢泼德
Original assignee: Fisons Ltd
Current assignee: Fisons Ltd
Priority date: 1995-06-29
Filing date: 1996-06-28
Publication date: 2003-12-10
Anticipated expiration: 2016-06-28
Also published as: IL122517A0; JPH11508458A; DE69608561D1; JP3806147B2; EP0835149B1; BR9608723A; NO315969B1; RU2137510C1; PL324316A1; CZ408997A3; GR3034141T3; PL182513B1; CN1189781A; KR19990028481A; EP0835149A1; GB9513218D0; HU220290B; CA2225750C; ATE193217T1; DE69608561T2

Abstract

An inhalation device comprising a chamber having an inlet and an outlet; and an active substance reservoir; wherein the device further includes vacuum means for forming a vacuum in the chamber and valve means arranged to release the vacuum, so that the substance contained in the reservoir is dispersed in the chamber on release of the vacuum.

Description

INhalation device and method

The present invention relates to a kind of suction apparatus, particularly a kind of suction apparatus that is used to assist the various particularly Powdered antiasthmatic drug thing isoreactivity materials of user suction.

Known have multiple be used to award put the particularly suction apparatus of antiasthmatic drug thing of medicine.For this class medicine, suction is the best medicine approach of awarding, and is significantly less than dosage given when oral because need obtain the required anti-dosage of breathing heavily effect.In addition, some medicine is malabsorption in intestines and stomach.

Many suction apparatus are by means of a kind of gaseous propellant or a kind of gas-pressurized formation medicine spray feed such as freon.A shortcoming of this pressurization inhaler is that patient may have untoward reaction for propelling gas.Have again, pay close attention to about existing from the environmental nuisance of freon widely.

Be used for having developed many with the Powdered suction apparatus of putting certain active substance of awarding.Such as Fisons ' Spinhaler (registered trade mark), in British patent No 1122284, have illustrated; TURBUHALER (registered trade mark) has illustrated in US Patent No 4524769; And in european patent application No 407028 illustrated device, it is reported by user and when sucking, operated by the air-flow that device is caused.Therefore, the effectiveness of awarding medicine just depends on the strong ability that sucks of user, and this situation is undesirable, because all do not have ability enough to be engaged in suction forcefully such as child or the so many user of weak adult.

WO 92/04066 (Bisgaard) has disclosed a kind of " adjustment type chamber " device, comprises a chamber (or interlayer), and active substance can be inhaled into wherein becomes disperse state; And an interface tube, patient can suck active substance of disperse by its from chamber.Chamber is limited by a wallboard spare at least, this wallboard spare can move between the two positions, reach minimum volume and maximum volume respectively in these two position upper chamber, this chamber also comprises a thrust unit, be used to push movable wall spare and reach the position at its maximum volume place towards the disperse chamber, so as active substance from storage inspiration disperse chamber.

In above device, wallboard spare is a piston, and moving of piston can cause active substance to be sucked into the disperse chamber.

More than device is suffered from many shortcomings.In the use, the slippage action of medicine meeting overslaugh sealing and piston, thus cause dosage to change at any time.Another shortcoming is, the medicine powder amount depends on the piston stroke size, and this trip size may change between each time of device used, because just weak more near the terminal spring of piston stroke more, user will can be answered operated piston in the scope one.Secondly, this device benzene is heavy, thereby uses inconvenience.

The purpose of this invention is to provide a kind of suction apparatus that is used for the various active substances of disperse, this device does not need special gaseous propellant, and it is used to can be the user of all types, even the very low user of those inhalation flow rate.

According to the invention provides a kind of suction apparatus, comprise that one has the chamber of an inlet and an outlet, and an active substance storage; Wherein, this device also comprises vacuum equipment, is used for forming certain vacuum at chamber, and valving, is provided with to such an extent that can remove vacuum, so that when vacuum is removed, and is contained in material disperse in the storage among chamber.

Preferably, inlet is furnished with connecting device, be used for chamber is connected in the active substance storage, so that active substance is sucked into chamber and disperse when Vacuum solutions is removed.Preferably, this connecting device is a housing, storage is pressed into is fitted to described chamber.Be that connecting device is connected in chamber to storage to form a gastight basically sealing easily.

" vacuum " speech uses very loosely at this, refers to pressure below atmospheric pressure, generally is 700mbar.

Device of the present invention is particularly advantageous, because valving can guarantee the rapid releasing of vacuum.These characteristics are particularly advantageous, can realize the very effective disperse in chamber of respirable active substance because air is poured into chamber fast.Device of the present invention can produce 70% medicated powder disperse, rather than usually with common apparatus reached 30% disperse.Effective disperse of the powder that apparatus of the present invention can be accomplished is compared with known various devices, can produce the attritive powder granule that is easy to inspiration of greater number.

Preferably, valving comprises a hinged gate, and it can move the disarm state that active substance can be sucked into chamber from a sealing state that seals up inlet.In addition, this hinged gate is located on the one second chamber inlet, is one such as thromboembolism with holes.

Preferably, hinged gate is held in sealing state by a releasable buckle.

Preferably, hinged gate is biased to disarm state.In addition, gate is pushed open fully by air-flow and is maintained by a stop device, and is released subsequently to return sealing station.

Preferably, active substance is certain powdered drug, and storage is suitable for providing the medicated powder of certain dosage dosage easily.Medicine can include only a kind of effective ingredient, such as a kind of moisture absorption medicine.The various active component that can propose comprise sodium cromoglicate, sodium nedocromil, albuterol and terbutaline.We prefer medicine can comprise a kind of inert carrier in addition, particularly under the situation of the tight medicine agglomerate of tamping, because disperse characteristic is improved.Suitable inert carrier comprises saccharide, such as lactose.When having certain inert carrier, we prefer the granular size of the granular size of carrier greater than active component.Suitable granular size from 1 to the 10 μ m of loose powdered active component.

The various medicines that can propose are formed and are comprised the mixture that any above-mentioned active component combines with lactose, carrier depends on the various concrete material of existence to the ratio of active component, such as, 1: 1 mixture that has been found that sodium nedocromil or sodium cromoglicate and lactose is very favourable.

Advantageously, storage comprises a dry medicated powder inhaler.

Preferably, vacuum equipment comprises first chamber portion and second chamber portion, and both link together hermetically and can relatively move to each other and are formed at spatial volume within the chamber with increase, thereby cause certain vacuum.

Preferably, screw device is arranged on each chamber portion, thereby the space that is formed within the chamber can be increased by rotating another part with respect to a part.Generally, the volume of expection two turn overs (720 °) or more less after reach.Contrary or the similar device of the system that can be provided with makes the action counter-rotating between each circle to prevent vacuum state, disposes a rapid kickoff mechanism simultaneously with permission user handle assembly correcting action.

Preferably, screw thread design becomes a kind of multiple thread, both can disperse load, can make that also user is easy to re-assembly this device after device is disassembled because of cleaning.

Preferably, hinged gate is connected in connecting device, and connecting device is rotating, thereby the rotation of connecting device makes releasable buckle be disengaged and allow hinged gate to move to disarm state.In addition, a locking devicen that pivots is removed so that gate is discharged from the edge of hinged gate.

Preferably, releasable buckle comprises the tang device, is configured among the chamber and can engages with the part of hinged gate under sealing state.

According to a further aspect of the invention, provide a kind of diffusion method of the active substance that remains to be sucked, the method comprises:

Dispose the chamber that an active substance storage and has an inlet and an outlet;

In chamber, form certain vacuum; And

The starter gate valve door gear to be removing vacuum, thus be contained in active substance among the storage when removing vacuum disperse among chamber.

Preferably, the method comprises chamber is connected in the active substance storage, so that is contained in that active substance among the storage is sucked into chamber when Vacuum solutions is removed and disperse is come.

By starting after this device finishes the disperse of active substance, he can suck the disperse material by the chamber outlet at user, and this outlet preferably is made for an interface tube, has a face shield when needing, and disposes a check valve.This check valve can prevent the chamber of the humid air access to plant of breathing out, if active substance is powdered, this can be a problem; And can prevent that required dosage is blown device.

Be easily, the outlet of this device was located in the mouth of user before removing vacuum, because moving of chamber may be caused dust cloud impulse chamber wall portion after causing, thereby reduced the quantity of the active substance that can be inhaled into.

Each preferred embodiment of the present invention is present will only to be illustrated with reference to accompanying drawing by example, wherein:

Fig. 1 is a kind of part sectioned view that is used to connect the device of a dosage medicated powder dosage inhaler (MDPI) of the present invention;

Fig. 2 a and 2b show the device of Fig. 5 a to 5c;

Fig. 3 is the part sectioned view of the device of Fig. 2 a and 2b, shows that housing rotates to generate vacuum with respect to chamber;

Fig. 4 a and 4b are profiles, and the pressure that shows MDPI discharges or causes, so as in chamber the pulverous active substance of disperse;

Fig. 5 a, 5b and 5c are each profiles of the apparatus of the present invention under sealing state;

Fig. 6 a, 6b and 6c are Fig. 5 a, 5b under release conditions and each profile of 5c device;

Fig. 7 shows another vacuum equipment that comprises a plunger and spring structure;

Fig. 8 a and 8b show the vacuum equipment of other embodiment that comprise a finger operation or manual vacuum pump configuration; And

Fig. 9 shows the chamber shape of another embodiment of the present invention.

As shown in the figure, a preferred suction apparatus of the present invention comprises a two-piece type cylindrical cavity 1, has an inlet 2 and one outlet 3.Preferably, chamber two parts all are to be made by the material that a kind of trade name that comprises polypropylene and styrene-ethylene butylene-styrene (SBS) is Evoprene.

Two parts of cylinder are sealed by an inner rubber sealing member 1a, as shown in the figure.

Though chamber 1 is paintings one cylinder in Fig. 1 to 7, should be appreciated that some other chamber shape also is available.Another preferred chamber shape is shown in Fig. 9.As shown in the figure, this chamber comprises co-axial, opposed two truncated cone part FC and FC ', and they can be tightly connected in its bottom.

Inlet 2 forms a housing 4, has connecting device 5, one MDPI sucking fits wherein.

Housing 4 and connecting device can be in particular a concrete MDPI design, perhaps can adopt deformable material to make to adapt to different MDPI.

One air duct A is arranged between MDPI and the housing by each internal groove on the housing, shown in Fig. 5 a.The size of these grooves is so fixed that unlikely formation surpasses the formed restriction of remainder of device significantly for mobile restriction.

The interface tube 7 of MDPI is tight fits, and is gas-tight seal to housing preferably.

Housing 4 preferably is positioned among the cylinder groove of chamber, shown in Fig. 1 and 5a and 5b.

Housing 4 and the MDPI6 that couples together can do unidirectional rotation with respect to chamber by means of each finger grip sheet 8.Rotation in the opposite direction is subjected to the prevention of the contrary helical spring R of a system, and it can be expanded and be locked on the aperture of chamber 1.

One sealing ring 9 forms vacuum seal between housing 4 and chamber 1.But, other sealing devices such as the pieceable molding apparatus of two-piece type, can replace sealing ring when needing.

Shown in Fig. 5 b and 6b, a gate 10 is articulated in housing 4 and can presses closer rubber gate sealing member 11 and keep closing by means of being arranged on releasable buckle 12 that one on the chamber 1 be shaped as tang (tang) 13 in the 10a place.

Shown in Fig. 5 a and 6b, gate 10 is asymmetrical, so that when tang 13 is in a side of gate (Fig. 5 b), gate remains on closed condition.But, when housing progressively rotates, can lose engage (Fig. 6 b) suddenly with gate.Gate is subsequently because the effect of vacuum pressure reduction, and preferably under the assistance of the biasing device such such as spring 14, is forced into immediately to discharge or opening.

The further rotation of housing (after causing or discharging) can make tang 13 engage again and close gate 10 again, makes it to enter sealing state in order to reuse.

In use, MDPI6 is at first set up with the medicated powder of providing a dosage dosage and is imbedded housing 4.Each finger grip sheet 8 is rotated subsequently so that gate 10 is closed to sealing state, and makes tang 13 place the initiation position.This position is indicated to user by the escapement device 15 that is shown among Fig. 2 b, 4b, 5c and the 6c, and this device 15 is placed between the aperture 16 of housing 4 and chamber 1.

This escapement device is an advantage, because click can be felt/be heard to user when arriving at above-mentioned position.

In the illustrated embodiment, chamber 1 two parts relatively rotate with respect to each other and the helicoid of operating screw thread 17 can generate certain vacuum, as shown in Figure 3.Preferably, the volume of chamber increases to 750ml under vacuum from initial 550ml under atmospheric pressure.

The volume of 750ml is very easily, because this volume can be easy to be sucked by child, thereby device provides the active component of the dosage that each lung of sucking from chamber inhales easily.

Illustrated coarse thread three-start screw whenever turns at chamber two parts and can make the chamber length overall strengthen 52mm between two refundings.

For initiating device, the interface tube 18 in suction apparatus exit is held in the mouth or the eyes in mouth, and between each finger grip sheet 8 and each chamber fin 9, applied and push action, shown in Fig. 4 b.

This will discharge release and tang 13 will be disengaged with gate 10.So because the effect of vacuum pressure reduction, preferably by means of bias spring 14, gate 10 is forced into release conditions at once.

Potion medicated powder can be by the easy a kind of suspension cloud cluster that sucks of a user to form be transmitted in chamber effectively owing to the rapid injection of air among.Along with the carrying out of suction process, fresh air can be sucked into the inlet 2 of chamber 1 by MDPI6.In illustrated device, do not include independent inlet valve and make additional input air enter chamber, but if desired, can dispose a kind of like this inlet.If comprise a kind of like this inlet valve, it can arrange to such an extent that be opened very soon after device causes.

Interface tube 18 is furnished with a rubber or a polymer gate valve 18a commonly used, enters chamber 1 in order to the humid air that prevents any exhalation, and in order to before discharging, to keep vacuum always.

Though the above-mentioned one way screw thread vacuum equipment 17 that has is desirable especially, the reader who is familiar with specialty will appreciate that, generated certain vacuum and can adopt various other vacuum equipments to be achieved before causing in chamber.

Another kind comprises that in chamber the vacuum equipment of an one way spring 20 and plunger (or piston) 21 structures is shown among Fig. 7.

In this embodiment, plunger 21 pushing top springs 20, it discharges and then generates certain vacuum.One vacuum remover can be opened the gate valve and make active substance be diffused to the chamber the inside from storage such as releasable buckle (catch) (not shown).

In another embodiment, vacuum is generated by the multipass pump installation, shown in Fig. 8 a and 8b, comprise one independent manually or the vacuum pump of being furnished with chamber inlet valve and outlet valve of finger manipulation.

But, back two kinds of devices are not too convenient, because be difficult to dismounting and clean, and/or to compare with preferred screw-type vacuum equipment be that comparatively benzene is heavy.

This preferred embodiment was once used and was set forth in EP 0,407, a kind of known MDPIFisons ' ULTRAHALER among 028 A2 ^TMDone test.As a kind of suction powder medicaments (Filsons ' Tilade ^TM) effectiveness of apparatus of the present invention of supplementary means adopts a kind of multistage hydraulic shock device resemble the Astra-Copley impacter to do test in a known way.Testing equipment comprises a respiratory tract and lung analog, and makes the people can determine to reach what and size of the particle of each different parts of human body.

Test result is shown in table 1 and 2.Important results relates to the weight of the medicine that reaches S3, S4 and each position of filter, because these positions show the respirable drug moiety that is applied to user, that is its size can be breathed to reach the medication amount of required therapeutic effect in the lung bottom.

Table 1: cylindrical cavity

The position	The mg/ dosage at each position	The gross weight that every dosage reclaimed (mg)
The position	The mg/ dosage at each position	The gross weight that every dosage reclaimed (mg)	Upper conduit	0.057	1.877
Downcomer	0.022	Gross weight (mg) in every dosage cloud cluster	Upper conduit	0.057	1.877
Downcomer	0.022		The interface tube	0.065
Throat	0.159		The interface tube	0.065	1.733(92.33％)
Throat	0.159	S1	0.121	Every dosage 3,4 and filter in gross weight (mg)	1.733(92.33％)
S2	0.146	S1	0.121
S2	0.146	S3	0.371		1.307(69.63％)
S4	0.826	S3	0.371	Average injection weight (mg)	1.307(69.63％)
S4	0.826	Filter	0.110	Average injection weight (mg)	12.6

Table 2: chamber shape as shown in Figure 9

The position	The mg/ dosage at each position	The callable gross weight of every dosage (mg)
The position	The mg/ dosage at each position	The callable gross weight of every dosage (mg)	Upper conduit	0.024	1.309
Downcomer	0.036	Gross weight (mg) in every dosage cloud cluster	Upper conduit	0.024	1.309
Downcomer	0.036		The interface tube	0.041
Throat	0.068		The interface tube	0.041	1.208(92.28％)
Throat	0.068	S1	0.040	Every dosage 3,4 and cleaner in gross weight (mg)	1.208(92.28％)
S2	0.090	S1	0.040
S2	0.090	S3	0.285		1.010(77.16％)
S4	0.692	S3	0.285	Average injection weight (mg)	1.010(77.16％)
S4	0.692	Filter	0.033	Average injection weight (mg)	11.5

These results show that the medicated powder dosage above 90% sucks and arrive the throat of user from chamber, and about 70% to 80% this spice has the size of arrived in lungs bottom as might be expected.

Co-axial, opposed two the frustoconical chamber portions that are shown in Fig. 9 are effective especially.This may be because, this shape relatively is suitable for the shape of dispersing the medicated powder cloud cluster that produced when vacuum is removed, that is the inhaling of medicated powder cloud cluster exhaled the wall portion of impulse chamber tempestuously that partly can not resemble its impact cylindrical cavity.Compare with cylindrical cavity, this can make the breathed part of more medicine cloud cluster be inhaled into from chamber.

Apparatus of the present invention are particularly meaning that user unlikely suffers the harm of the possible side effect of medicine to the effectiveness of medicament administration required therapentic part in the user body in the powder mode.This just makes this device be especially suitable for use as a kind of suction auxiliary device of various types of sterin (steroidal) medicine, and these medicines it is reported it is to produce adverse side effect.

Claims

1. a suction apparatus comprises: the chamber with an inlet and an outlet; An active substance storage; And the vacuum equipment that is used for forming vacuum at described chamber; In order to remove the valving of vacuum; And the connecting device that is used for described chamber is connected in the active substance storage; It is characterized in that:

Active substance be a kind of dry powdered and with dried powder give with, and storage is suitable for the medicated powder of a kind of dosage of disperse; And

Be contained in that material in the storage is sucked into chamber when vacuum is removed and disperse is therein come.

2. according to the described device of claim 1, wherein, described valving comprises a hinged gate, and it can be transformed into a disarm state from a sealing state that seals described inlet.

3. according to the described device of claim 1, wherein, storage comprises a dry medicated powder inhaler.

4. according to the described device of claim 1, wherein, connecting device comprises that one is pressed into the device that is connected.

5. according to the described device of claim 1, wherein, continuous apparatus is connected in described chamber to storage to form a gas-tight seal basically.

6. according to the described device of claim 1, wherein, vacuum equipment comprises an one way spring and a piston structure.

7. according to the described device of claim 1, wherein, vacuum equipment comprises a multipass pump.

8. according to the described device of claim 2, wherein, hinged gate remains on a sealing state by means of a releasable buckle.

9. according to the described device of claim 8, wherein, hinged gate is biased into disarm state.

10. according to the described device of claim 8, wherein, releasable buckle comprises a tang device, and this tang device is arranged in the described chamber and at sealing state and engages with the part of hinged gate.

11. according to the described device of claim 10, wherein, hinged gate is connected in described connecting device, and connecting device is rotating, thereby the rotation of connecting device makes releasable buckle be disengaged and allow hinged gate to move to disarm state.

12. according to the described device of claim 1, wherein, vacuum equipment comprises each chamber portion, also causes certain vacuum thereby each chamber portion links together hermetically and can increase the spatial volume that is defined in the chamber each other with relatively moving.

13. according to the described device of claim 1, wherein, screw device is arranged on each chamber portion, thereby the space that is defined within the chamber can be increased by the each several part that relatively rotates with respect to each other.

14. the diffusion method of an active substance that remains to be sucked, the method comprises:

Dispose an active substance storage, be suitable for the dry medicated powder of a kind of dosage dosage of disperse;

Configuration one has the chamber of an inlet and an outlet;

Chamber is connected in the active substance storage;

Form certain vacuum in the air in the chamber; And

The starter gate valve door gear to be removing vacuum, thus encourage the active substance that is placed in the storage when vacuum is removed in chamber disperse come.

15. in accordance with the method for claim 14, wherein, active substance is a kind of moisture absorption medicine.

16. in accordance with the method for claim 15, wherein, the moisture absorption medicine is selected from the sour sodium of color, sodium nedocromil, albuterol and terbutaline.